Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Aug;19(8):1159-66.
doi: 10.1016/j.bbmt.2013.04.026. Epub 2013 May 6.

Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation

Cara L McDermott  1 , Brenda M Sandmaier, Barry Storer, Hong Li, Donald E Mager, Michael J Boeckh, Meagan J Bemer, Jennifer Knutson, Jeannine S McCune
Affiliations

Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation

Cara L McDermott et al. Biol Blood Marrow Transplant. 2013 Aug.

Abstract

We evaluated the pharmacodynamic relationships between mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and outcomes in 308 patients after nonmyeloablative hematopoietic cell transplantation. Patients were conditioned with total body irradiation ± fludarabine, received grafts from HLA-matched related (n = 132) or unrelated (n = 176) donors, and received postgrafting immunosuppression with MMF and a calcineurin inhibitor. Total and unbound MPA pharmacokinetics were determined to day 25; maximum a posteriori Bayesian estimators were used to estimate total MPA concentration at steady state (Css). Rejection occurred in 9 patients, 8 of whom had a total MPA Css less than 3 μg/mL. In patients receiving a related donor graft, MPA Css was not associated with clinical outcomes. In patients receiving an unrelated donor graft, low total MPA Css was associated with increased grades III to IV acute graft-versus-host disease and increased nonrelapse mortality but not with day 28 T cell chimerism, disease relapse, cytomegalovirus reactivation, or overall survival. We conclude that higher initial oral MMF doses and subsequent targeting of total MPA Css to greater than 2.96 μg/mL could lower grades III to IV acute graft-versus-host disease and nonrelapse mortality in patients receiving an unrelated donor graft.

Keywords: Bayesian; Graft versus host disease; Hematopoietic cell transplant; Mycophenolic acid; Pharmacokinetics.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Association of total MPA Css with grades 3–4 acute GVHD (A) and non-relapse mortality (B) after day 25 in unrelated donor G-PBMC grafts
MPA Css is the average of all values from day 0 through day 25. Total MPA Css values are lower quartile (0.61 to 1.76 μg/mL), interquartile range (1.77 to 2.96 μg/mL), and upper quartile (2.97 to 4.6 μg/mL).
Figure 2
Figure 2. Lack of association of total MPA Css with grades 3–4 acute GVHD (A) and non-relapse mortality (B) after day 25 in related donor G-PBMC grafts
MPA Css is the average of all values from days 0 through 25. Total MPA Css values are lower quartile (0.61 to 1.76 μg/mL), interquartile range (1.77 to 2.96 μg/mL), and upper quartile (2.97 to 4.6 μg/mL).
Figure 3
Figure 3. Lack of association between MPA Css, both total (A, B) and unbound (C, D), with day 28 donor T-cell chimerism in related (A, C) and unrelated (B,D) donor PSBC grafts
MPA Css is the average of all values from days 0 through 25.
See this image and copyright information in PMC

References

    1. Mineishi S. Overcoming the age barrier in hematopoietic stem cell transplantation: progress, but still a long way to go. Jama. 2011;306:1918–1920. - PubMed
    1. Sorror ML, Sandmaier BM, Storer BE, et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. Jama. 2011;306:1874–1883. - PMC - PubMed
    1. Maris MB, Niederwieser D, Sandmaier BM, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003;102:2021–2030. - PubMed
    1. Nash RA, Johnston L, Parker P, et al. A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005;11:495–505. - PubMed
    1. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin Pharmacokinet. 2007;46:13–58. - PubMed

Publication types

MeSH terms

Substances